SARS-CoV-2 mRNA Vaccines Induce Cross-Reactive Antibodies to NL63 Coronavirus but Do Not Boost Pre-Existing Immunity Anti-NL63 Antibody Responses

Background/Objectives: mRNA vaccines have demonstrated strong immunogenicity and efficacy against SARS-CoV-2. However, the extent of antibody cross-reactivity against human seasonal coronaviruses, such as NL63, remains unclear. Furthermore, it is unknown whether pre-existing antibody responses against NL63 might influence the outcome of SARS-CoV-2 mRNA vaccination. Methods: We used a flow cytometry-based serological assay and an in vitro neutralization assay to analyze NL63 antibody responses in sera from SARS-CoV-2 mRNA-vaccinated mice and plasma samples from a vaccinated human cohort. Results: We found that the Moderna mRNA-1273 vaccine can generate cross-reactive antibodies against NL63. Importantly, SARS-CoV-2 mRNA vaccination did not boost pre-existing anti-NL63 responses in humans, and pre-existing NL63 antibody levels did not affect the antibody response induced by SARS-CoV-2 mRNA vaccination. Conclusions: These findings suggest that while SARS-CoV-2 mRNA vaccination can induce cross-reactive antibodies against NL63, pre-existing immunity to this seasonal coronavirus does not appear to significantly impact vaccine immunogenicity. These findings contribute to our understanding of the complex interplay between pre-existing immunity to seasonal coronaviruses and the immune response generated by SARS-CoV-2 mRNA vaccines.